Heparin and SARS-CoV-2: Multiple Pathophysiological Links.

Low molecular weight heparin, enoxaparin, has been one of most used drugs to fight the SARS-CoV-2 pandemic. Pharmacological properties of heparin recognize its specific ability, as with other oligosaccharides and glycosaminoglycan, to bind several types of viruses during their pass through the extracellular matrix of the respiratory tract, as well as its anticoagulant activity to prevent venous thromboembolism. Antithrombotic actions of enoxaparin have been testified both for inpatients with COVID-19 in regular ward and for inpatients in Intensive Care Units (ICUs). Prophylactic doses seem to be able to prevent venous thromboembolism (VTE) in inpatients in the regular ward, while intermediate or therapeutic doses have been frequently adopted for inpatients with COVID-19 in ICU. On the other hand, although we reported several useful actions of heparin for inpatients with COVID-19, an increased rate of bleeding has been recorded, and it may be related to several conditions such as underlying diseases with increased risks of bleeding, increased doses or prolonged administration of heparin, personal trend to bleed, and so on.

Blood Targets of Adjuvant Drugs Against COVID19.

While waiting for the vaccine and/or the best treatment for COVID19, several drugs have been identified as potential adjuvant drugs to counteract the viral action. Several drugs, in fact, have been suggested for their ancillary antiviral role. Viral proteases and peptidases, may interact with well-known drugs such as anticoagulants, antihypertensives, antiserotoninergics and immunomodulants. We here report a basic list of these drugs that include bioflavonoids, heparinoids, ACE inhibitors, angiotensin receptor blockers, antiserotoninergics, and monoclonal antibodies against cytokines that may interact with the viral cycle.

SV-IV Peptide1-16 reduces coagulant power in normal Factor V and Factor V Leiden.

Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance. Factor V Leiden (FVL) disorder may lead to thrombophilia. Whether a reduction in the activation of Factor V or Factor V Leiden may correct the disposition to thrombophilia is unknown. Therefore we tested SV-IV Peptide 1-16 (i.e. a peptide derived by seminal protein vescicle number IV, SV-IV) to assess its capacity to inhibit the procoagulant activity of normal clotting factor V or Factor V Leiden (FVL). We found that SV-IV protein has potent anti-inflammatory and immunomodulatory properties and also exerts procoagulant activity. In the present work we show that the SV-IV Peptide 1-16, incubated with plasma containing normal Factor V or FVL plasma for 5 minutes reduces the procoagulant capacity of both substances. This is an anticoagulant effect whereas SV-IV protein is a procoagulant. This activity is effective both in terms of the coagulation tests, where coagulation times are increased, and in terms of biochemical tests conducted with purified molecules, where Factor X activation is reduced. Peptide 1-16 was, in the pure molecule system, first incubated for 5 minutes with purified Factor V then it was added to the mix of phosphatidylserine, Ca2+, Factor X and its chromogenic molecule Chromozym X. We observed a more than 50% reduction in lysis of chromogenic molecule Chromozym X by Factor Xa, compared to the sample without Peptide 1-16. Such reduction in Chromozym X lysis, is explained with the reduced activation of Factor X by partial inactivation of Factor V by Peptide 1-16. Thus our study demonstrates that Peptide 1-16 reduces the coagulation capacity of Factor V and Factor V Leiden in vitro, and, in turn, causes factor X reduced activation.

Rate and duration of hospitalization for deep vein thrombosis and pulmonary embolism in real-world clinical practice.

BACKGROUND: Current guidelines recommend initial treatment with anticoagulants at home in patients with acute deep vein thrombosis (DVT) and in patients with low-risk pulmonary embolism (PE) with adequate home circumstances. However, most of the patients with acute venous thromboembolism (VTE) are currently hospitalized regardless of their risk of short-term complications. AIM OF THE STUDY: To assess the proportion of outpatients with acute VTE initially treated in hospitals, to assess the mean duration of hospitalization, and to identify predictors for in-hospital or home treatment. METHODS: Data of Italian patients enrolled in the RIETE registry from January 2006 to December 2013 were included. RESULTS: Altogether 766 PE and 1,452 isolated DVT were included. Among PE patients, mean PESI score was 84 points (SD 35), and 56% of patients had a low-risk PESI score (<85). In all, 53.7% of DVT and 17.0% of PE were entirely treated at home, and 38.2% of DVT patients and 19.9% of PE patients were hospitalized for ≤5 days. On multivariate analysis, low PESI score was not independently associated with the hospitalization of PE patients. CONCLUSIONS: One in every two patients with DVT and five in every six with PE are still hospitalized.

Anti-thrombin action of low-dose acetylsalicylic acid.

It is known that low-dose aspirin is effective in coronary artery therapy, although it has not yet been clarified how it exerts its action. Here, we report that treatment of coronary artery patients with 100 mg/day of aspirin does not attenuate thrombin generation, but reduces free thrombin by favouring the formation of thrombin/antithrombin (TAT) complexes. Antithrombin hyperactivation is mediated by inhibition of platelet factor 4 release from alpha-granules, leading to higher heparin availability.